Docking of sialic acid analogues against influenza A hemagglutinin: a correlational study between experimentally measured and computationally estimated affinities
A molecular docking tool of AutoDock3.05 was evaluated for its ability to reproduce experimentally determined affinities of various sialic acid analogues toward hemagglutinin of influenza A virus. With the exception of those with a C6-modified glycerol side chain, the experimental binding affinities of most sialic acid analogues (C2, C4 and C5-substituted) determined by viral hemadsorption inhibition assay, hemagglutination inhibition assay and nuclear magnetic resonance correlated well with the computationally estimated free energy of binding. Sialic acid analogues with modified glycerol side chains showed only poor correlation between the experimentally determined hemagglutinin inhibitor affinities and AutoDock3.05 scores, suggesting high mobility of the glutamic acid side chain at the glycerol binding pocket, which is difficult to simulate using a flexi-rigid molecular docking approach. In conclusion, except for some glycerol-substituted sialic acid analogues, the results showed the effectiveness of AutoDock3.05 searching and scoring functions in estimating affinities of sialic acid analogues toward influenza A hemagglutinin, making it a reliable tool for screening a database of virtually designed sialic acid analogues for hemagglutinin inhibitors.
KeywordsHemagglutinin Sialic acid analogues Molecular docking Affinity
- 9.Hurt AC, Ernest J, Deng Y-M, Iannello P, Besselaar TG, Birch C, Buchy P, Chittaganpitch M, Chiu S-C, Dwyer D, Guigon A, Harrower B, Kei IP, Kok T, Lin C, McPhie K, Mohd A, Olveda R, Panayotou T, Rawlinson W et al (2009) Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa. Antivir Res 83:90–93CrossRefGoogle Scholar
- 11.Sauter NK, Hanson JE, Glick GD, Brown JH, Crowther RL, Park SJ, Skehel JJ, Wiley DC (1992) Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography. Biochemistry 31:9609–9621CrossRefGoogle Scholar
- 12.Sauter NK, Bednarski MD, Wurzburg BA, Hanson JE, Whitesides GM, Skehel JJ, Wiley DC (1989) Hemagglutinins from two influenza virus variants bind to sialic acid derivatives with millimolar dissociation constants: a 500 MHz proton nuclear magnetic resonance study. Biochemistry 28:8388–8396CrossRefGoogle Scholar
- 15.Pritchett TJ (1987) Receptor analogue inhibitors of influenza virus adsorption and infection. PhD thesis, University of California, Los AngelesGoogle Scholar
- 18.Al-Qattan MN, Mordi MN (2009) Site-directed fragment-based generation of virtual sialic acid databases against influenza A hemagglutinin. J Mol Model (in press) online first: doi:10.1007/s00894-009-0606-y